1Alpha, 25 dihydroxyvitamin D3-dependent up-regulation of calcium-binding proteins in motoneuron cells.
Our understanding of selective neuronal vulnerability as well as etiopathogenesis of sporadic neurodegenerative diseases is extremely limited. In ALS, altered calcium homeostasis appears to contribute significantly to selective neuronal injury. Further in ALS, the absence of calcium binding proteins (calbindin-D28K, parvalbumin, and calretinin) correlates with selective vulnerability and cell loss. In motoneuron cell culture models an ALS IgG-triggered and calcium-mediated destruction can be reversed by increased expression of calbindin-D28K following retroviral infection with calbindin-D28K cDNA. To increase calcium binding protein expression in motoneurons in vitro and in vivo, we have employed vitamin D3. Forty-eight hr treatment of differentiated VSC 4.1 cells with 0.1-30 nM 1,25 dihydroxyvitamin D3 induced a two-fold increase in the immunoreactivity for calbindin-D28K and parvalbumin. Injection of 80-120 ng, 1,25 dihydroxyvitamin D3 in the cerebral ventricles of adult rats also induced positive immunoreactivity for calcium binding proteins in ventral motoneurons which are completely devoid of such reactivity in the adult stage. These data suggest that analogs of 1,25 dihydroxyvitamin D3 may be useful tools in enhancing the expression of calcium binding proteins in the motor system and may have possible therapeutic value in neurodegenerative disease.
Alexianu
M E
ME
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
Robbins
E
E
Carswell
S
S
Appel
S H
SH
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D002117:Calcitriol